Having found several shortcomings in my previous post on this subject I
have decided to take a different approach. Let's compare Eph 5:18 with
John the Baptist's prophecy about baptism in/with/by the Spirit
(Matthew: 3:11, Mark 1:8, Luke 3:16, John 1:33, Acts 1:5, Acts 11:16).
All these six references contain some form of:

baptizw ---> en pneumati

In Eph 5:18 we have:

plhrousthe ---> en pneumati

Now my argument is that in both examples we have a dominate semantic
element which is the verb. What I am saying is, the verb dictates what
the prepositional phrase can and does mean.

Furthermore, both of these cases involve a comparison, a parallel
comparison of the form: *this is like that*. In John the Baptist's
prophecy, he compares his water baptism to Spirit baptism.

So if we combine the dominant semantic element, the verb baptism with
the: *this is like that* comparison we come up with a rather limited
range of possible meanings for the phrase: en pneumati.

In Eph 5:18 we have a comparison between drinking two much wine and
being Spirit filled. If we take the meaning of the semantically dominant
verb plhrousthe and combine it with the comparison we will come up with
a rather limited range of possible meanings for the phrase: en pneumati.

I would concluded from the above analysis that en pneumati when used
with baptizw is going to have a meaning governed by the semantic value
of baptizw in this context.

In like manner I would conclude that hat en pneumati when used with
plhrousthe is going to have a meaning governed by the semantic value of
plhrousthe in this context.

If this is all too hypothetical for some folks, let's be plain. Wine
goes inside you and you become drunk. This is the first half of the
comparison. Secondly, you should avoid being drunk but rather be filled
(goes inside you, second half of comparison) with the Spirit.

The **main point** I am trying to make is that an argument using the
pattern *RE: EN + dative* to drive the exegesis of this passage is
letting the tail wag the dog. The pattern *RE: EN + dative* is not the
dominate semantic element and the above explanation is not syntactically
or semantically impossible.